The purpose of this project is to provide the means and methodology by which some of the major determinants of the effectiveness of various cancer therapies (hyperthermia, radiation and chemo) may be isolated and identified. Factors at the local tissue level which are recognized as central to the tumoricidal action of these therapies, either alone or in combination, include: temperature, perfusion, oxygen tension, tissue thermal conductivity and diffusivity, and specific absorption rate. These quantities will be measured using both the enhanced thermal diffusion probe (ETDP) and the multisensor Profilometer instrumentation systems. The first objective of this project is to integrate the ETDP and Profilometer systems into the scanned, intensity modulated, focused ultrasound (SIMFU) hyperthermia delivery system to provide 1) improved thermal dosimetric capabilities for pre- therapy predictive and post-therapy reconstructive thermal modeling, and 2) the necessary density of measurement information from a limited number of invasive proves to allow realistic spatio-temporal monitoring and control of treatment temperature uniformity. The second objective is to examine the temporal and spatial dependence of perfusion and oxygen tension in normal and tumor tissue, under normo- and hyperthermia, and under the influence of other stimuli such as anesthesia. In one series of experiments, uniform temperature elevations in relatively large tissue volumes will be generated by the SIMFU system and controlled by means of multiple tissue temperature measurements with the Profilometer. Power requirements and tissue temperature variations will be monitored and related to bulk and local perfusion variations. This approach combines both the generation of tissue hyperthermia and measurement of of its effects into a unified experimental procedure. In related, concurrent experiments, the ETDP and Profilometer will be used to simultaneously measure tissue perfusion, oxygen tension, and other properties during various clinical interventions. This project makes possible local, multiple measurements of these crucial tissue properties, providing the means to examine their interrelationships and the thermal dosimetry essential for the improvement of the clinical hyperthermia systems in this PPG.